The goal of this proposal is to determine how genetic and epigenetic influences modulate mandibular skeletogenesis. How ECM molecules and growth factors influence or contribute to mandibular pattern formation is the main focus of this proposal. Our previous data indicate that ectomesenchymal cells have chondrogenic potential as early as stage HH 16. We will determine when and how mesencephalic neural crest (NC) cells acquire their chondrogenic potential. The influence of the ECM on differentiation of these cells will be examined. The expression of type II collagen, tenascin, fibronectin, and TGF B mRNAs by NC cells will be examined and correlated with their differentiation potential. Unlike the limb bud, the regions involved in outgrowth and pattern formation in the developing mandibles are not identified. We propose to identify such region(s) by examining the temporal and spatial expression of homeobox- containing genes and by identifying proliferating zones in the mandibular arch. Our previous data show that the mandibular epithelium inhibits chondrogenesis in spatial organization of Meckel's cartilage (MC) in vivo we will examine the chondrogenic potential of the mesenchyme cells from non-chondrogenic regions of the mandible. We will examine the effect of retinoic acid, TGF B'S and bFGF on chondrogenesis and the expression of ECM molecules in vitro using by dot blot hybridization or PCR analysis. These effects will be compared with the mesenchymal cell response to mandibular epithelium. We will determine whether mandibular mesenchyme during chondrogenesis. Finally, avian MC is unique since it persists into adult life. We will investigate the role of tissue environments in promoting or inhibiting ossification using chick/quail chimeric grafts. Finally, because of the unique difference between avian and mammalian MC, we will examine the epithelio-mesenchymal interactions and begin to map the expression of ECM molecules during chondrogenesis, resorption and ossification in the mouse mandibular arch.